This phase I clinical trial （NCT01935843） is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell （CART） immunotherapy tar- geting human epidermal growth factor receptor...This phase I clinical trial （NCT01935843） is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell （CART） immunotherapy tar- geting human epidermal growth factor receptor 2 （HER2） in patients with advanced biliary tract cancers （BTCs） and pancreatic cancers （PCs）. Eligible patients with HER2-positive （〉50%） BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab- paclitaxel （100-200 mg/m2） and cyclophosphamide （15-35 mglkg）. CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART- HER2 cell infusion （median CAR＋ T cell 2.1× 10^6/kg）. The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgialarthralgia, and lym- phopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase （〉9 ULN）, adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastroin- testinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1-2delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months （range, 1.5-8.3 months）. Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encourag- ing signals of clinical activity.展开更多
针对传统的遥感影像解译速度缓慢、效率较低、人力物力需求量大等问题,基于谷歌地球引擎(Google Earth Engine,GEE)平台,利用Landsat TM/OLI遥感影像,采用分类回归树(Classification and Regression Tree,CART)方法,对1990~2016年北京...针对传统的遥感影像解译速度缓慢、效率较低、人力物力需求量大等问题,基于谷歌地球引擎(Google Earth Engine,GEE)平台,利用Landsat TM/OLI遥感影像,采用分类回归树(Classification and Regression Tree,CART)方法,对1990~2016年北京市土地覆被/土地利用变化(LUCC,Land Use and Land Cover Change)开展了遥感解译研究,分析了北京市土地覆被/土地利用时空动态变化特征和耕地、人造地表面积变化的驱动机制。研究表明:(1)GEE在区域尺度遥感数据分析和处理等方面具有方便快捷的优势。(2)CART方法进行遥感分类精度较高,研究所得的6期土地覆被/利用数据产品与训练样本交叉验证的学习精度均在93%以上,方法可靠有效。2010年的分类产品与测试样本混淆矩阵的验证精度为88.67%,Kappa系数为0.86。2010年的分类产品与GlobeLand30-2010数据的空间一致性为74.0%,其中林地一致性高达84.28%;两套产品中,人造地表、草地和水体面积比重相差不足1%,各地类面积构成一致性较高。(3)北京市主要土地类型为耕地、林地和人造地表,面积比重为90%左右;1990~2016年期间人造地表和林地面积呈增加态势,耕地和水体呈萎缩态势,其中,人造地表面积增加1 371km2,增幅高达87%以上,耕地萎缩幅度近40%;1990~2016年北京市平原地区人造地表由圈层状的"摊大饼"扩张态势向"遍地开花"扩张态势转变;人造地表的扩张主要通过对耕地的侵占实现。人口快速增长、经济快速发展以及政策等社会经济发展因素驱动北京市土地覆被/土地利用的演化进程。展开更多
基金We would like to thank all patients who participated in this trial. This study was supported by the grants from the National Natural Science Foundation of China （Grant No. 81230061 to WDH）, the Science and Technology Planning Project of Beijing City （No. Z151100003915076 to WDH）, the National Key Research and Development Program of China （Nos. 2016YFC1303501 and 2016YFC1303504 to WDH）.
文摘This phase I clinical trial （NCT01935843） is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell （CART） immunotherapy tar- geting human epidermal growth factor receptor 2 （HER2） in patients with advanced biliary tract cancers （BTCs） and pancreatic cancers （PCs）. Eligible patients with HER2-positive （〉50%） BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab- paclitaxel （100-200 mg/m2） and cyclophosphamide （15-35 mglkg）. CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART- HER2 cell infusion （median CAR＋ T cell 2.1× 10^6/kg）. The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgialarthralgia, and lym- phopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase （〉9 ULN）, adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastroin- testinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1-2delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months （range, 1.5-8.3 months）. Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encourag- ing signals of clinical activity.
文摘针对传统的遥感影像解译速度缓慢、效率较低、人力物力需求量大等问题,基于谷歌地球引擎(Google Earth Engine,GEE)平台,利用Landsat TM/OLI遥感影像,采用分类回归树(Classification and Regression Tree,CART)方法,对1990~2016年北京市土地覆被/土地利用变化(LUCC,Land Use and Land Cover Change)开展了遥感解译研究,分析了北京市土地覆被/土地利用时空动态变化特征和耕地、人造地表面积变化的驱动机制。研究表明:(1)GEE在区域尺度遥感数据分析和处理等方面具有方便快捷的优势。(2)CART方法进行遥感分类精度较高,研究所得的6期土地覆被/利用数据产品与训练样本交叉验证的学习精度均在93%以上,方法可靠有效。2010年的分类产品与测试样本混淆矩阵的验证精度为88.67%,Kappa系数为0.86。2010年的分类产品与GlobeLand30-2010数据的空间一致性为74.0%,其中林地一致性高达84.28%;两套产品中,人造地表、草地和水体面积比重相差不足1%,各地类面积构成一致性较高。(3)北京市主要土地类型为耕地、林地和人造地表,面积比重为90%左右;1990~2016年期间人造地表和林地面积呈增加态势,耕地和水体呈萎缩态势,其中,人造地表面积增加1 371km2,增幅高达87%以上,耕地萎缩幅度近40%;1990~2016年北京市平原地区人造地表由圈层状的"摊大饼"扩张态势向"遍地开花"扩张态势转变;人造地表的扩张主要通过对耕地的侵占实现。人口快速增长、经济快速发展以及政策等社会经济发展因素驱动北京市土地覆被/土地利用的演化进程。
